Epidemiologic studies and clinical registries have reported that chronic kidney disease (CKD) has a discrete increasing prevalence but it is clear that patients with CKD are a heterogeneous group with different diagnosis, diverse disease etiologies, variable prognosis and markedly diverse rate of progressive decline (1, 2) (3). CKD is thought traditionally to follow an unremittingly progressive decline over time, with often an inconstant rate of decline, and even increases in baseline renal function (glomerular filtration rate (GFR)) may also be common(4) (5). Several studies identified risk factors for CKD progression or increased renal function loss, however it is also recognized that only a relatively small percentage of the individuals with CKD eventually progress to end-stage renal disease (ESRD).
Renal disease progression may follow linear and non-linear trajectories with only a minority accelerating swiftly to end-stage kidney disease (6). The prediction of speed or change in disease progression is a challenging disease characteristic to forecast. Nevertheless the ability to identify those individuals at greatest risk of progression that may require intensification of standard therapy from those at low risk to be spared unnecessary intervention may well be the cornerstone strategy to overcome the current limitations in renal clinical development. From a clinical and therapeutic point of view, early detection of fast progressing patients allows a closer monitoring of both adherence and therapeutic efficacy and may guide intensification of standard therapy (7-9). From a drug development perspective, being able to distinguish patients with an increased risk of disease progression from those patients with a lower risk is an essential step for increasing the probability of success and impact of a novel therapeutic approach.
Such a patient stratification protocol would result in increased efficacy with acceptable safety within a desirable development timeframe. Clinical nephrology has suffered so far of the lack of those concrete tools to identify distinct disease dynamic changes that inevitably would help clinical decision making, promote novel therapeutic approaches and bring innovation in the design of Proof-of-Concept (PoC) clinical studies.
Therefore there is a compelling clinical need for novel risk scores, clinical predictors and/or biomarkers to identify individuals with an increased risk of CKD disease progression at the earliest possible stage (11) (12). The need for risk stratification within CKD is particularly great among patients in the general population or primary care because the majority of patients with CKD are first identified in this setting and most are never referred to a nephrologist.